Lack of association between the CALM1 core promoter polymorphism (-16C/T) and susceptibility to knee osteoarthritis in a Chinese Han population

Dongquan Shi,Yong Xu,Lunqing Zhu,Chen Yao,Dongyang Chen,Zhenxing Shao,Jin Dai,Jianghui Qin,Haijian Ni,Long Yi,Zhihong Xu,Shiro Ikegawa,Qing Jiang

doi:10.1186/1471-2350-9-91

Abstract

BackgroundCALM1 gene encodes calmodulin (CaM), an important and ubiquitous eukaryotic Ca2+-binding protein. Several studies have indicated that a deficient CaM function is likely to be involved in the pathogenesis of osteoarthritis (OA). Using a convincing genome-wide association study, a Japanese group has recently demonstrated a genetic association between the CALM1 core promoter polymorphism (-16C/T transition SNP, rs12885713) and OA susceptibility. However, the subsequent association studies failed to provide consistent results in OA patients of differently selected populations. The present study is to evaluate the association of the -16C/T polymorphism with knee OA in a Chinese Han population.MethodsA case-control association study was conducted. The polymorphism was genotyped in 183 patients who had primary symptomatic knee OA with radiographic confirmation and in 210 matched controls. Allelic and genotypic frequencies were compared between patients and control subjects.ResultsNo significant difference was detected in genotype or allele distribution between knee OA and control groups (all P > 0.05). The association was also negative even after stratification by sex. Furthermore, no association between the -16C/T SNP genotype and the clinical variables age, sex, BMI (body mass index) and K/L (Kellgren/Lawrence) score was observed in OA patients.ConclusionThe present study suggests that the CALM1 core promoter polymorphism -16C/T is not a risk factor for knee OA susceptibility in the Chinese Han population. Further studies are needed to give a global view of this polymorphism in pathogenesis of OA.

Highlights

Calmodulin 1 gene (CALM1) gene encodes calmodulin (CaM), an important and ubiquitous eukaryotic Ca2+-binding protein
Through a large-scale association study with subsequent functional researches, the Japanese group have demonstrated a convincing association between the CALM1 core promoter polymorphism and Japanese hip OA
The well clarified role Ca2+-calmodulin signal played in chondrogenesis and normal cartilage phenotype maintaining, together with the results of the microarray analysis [7] showing higher levels of CALM1 expression both in hip and knee OA, have interested us in assessing whether this genetic polymorphism is associated with OA in a Chinese Han population

Summary

Introduction

CALM1 gene encodes calmodulin (CaM), an important and ubiquitous eukaryotic Ca2+-binding protein. Osteoarthritis (OA) is a common musculoskeletal disease among the elderly, characterized by the degradation of articular cartilage and formation of abnormal bone (osteophyte). It is a multifactorial disorder in which aging, genetic, hormonal and mechanical factors are all major contributors to its onset and progression [1]. Results of family-based and candidate gene studies have demonstrated a clear genetic component, for earlyonset OA [2,3,4]. The identification of candidate genes for OA susceptibility has mainly focused on genes encoding collagens ( for type II collagen), for other structural proteins of the extracellular cartilage matrix(ECM), the vitamin D and estrogen receptor genes, and for bone and cartilage growth factors [5]. The specific underlying genetic factors and mechanisms in the development of osteoarthritis need to be further researched

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